Quaternary ammonium germ counteracting agents



Patented May 11, 1954 QUATERNARY AMMONIUM GERM GOUNTERACTING AGENTSBenjamin B. Harris, Glencoe, 111., assignor to The Emulsol Corporation,Chicago, 111., a corporation of Illinois N Drawing. Application August21, 1952,

Serial No. 305,710

7 Claims. (01. 260-290) T s invention es to nteracting Illustrativegerm-counteracting agents falling agents and to compositions forcounteracting the within the scope of the invention are the followefiectof various microorganisms, said agents ing: and compositions beinghighly useful for bactericidal, germicidal, bacteriostatic,prophylactic, 5 (I) C OH antiseptic and fungicidal purposes which, forconvenience, are hereafter referred to as germ-coun- Br teracting agentsand compositions. The germ- C1 counteracting compositions of the presentinvention contain, as an effective germ-counter- (2) OIHHOOHPN actingagent, certain agents or compounds, or mixtures thereof, which can berepresented by the formulae (IV) OnHz,.+ --Ar CHPITTR2 1 CIH| A R: I V

a c H where R is an alkyl radical containing from 12 U p to 18 carbonatoms, at and y are integers not greater than 2, Ar is an aromatichydrocarbon p i radical such as a benzene or alkyl benzene radical, A isan anion, particularly one selected from the group consisting ofchlorine, bromine and (7) iodine, and R1, R2 and R3 are hydrocarbonradi- CaHI cals, particularly lower alkyl radicals such as methyl, ethyland propyl, each of R1, R2 and R3 CHHN advantageously containing no morethan 5 to 7 Br carbon atoms and together totaling no more than 10 carbonatoms, or R1, R2 and R3 together (8) with the nitrogen comprise aheterocyclic radi- 40 cal such as pyridine, quinoline or the like, and a1b is an integer from 12 to 18. Various of the like] more specificagents may be characterized as comprising quaternary ammonium compoundshaving attached to the quaternary nitrogen atom thereof (1) anacid-forming anion, for instance, halogen, (2) a hydrocarbon benzylgroup, ring substituted with from one to three alkyl groups, CH: one ofwhich contains from 11 to 16 or 12 to 18 ,,O Z carbon atoms and anyother one of which conl\ tains not over 4 carbon atoms, and (3) three 501 alkyl groups of notover 5 carbon atoms each, or I a trivalenthydrocarbon chain which jointly with the nitrogen forms a pyridine orpyridine CHI homologue heterocycle. I H| Germ-counteracting agentsfalling within the scope of the' invention maybe prepared by reacting anaromatic methyl halide, for example, benzyl chloride with an olefinunder alkylating conditions to .introduce an alkyl radical, or aplurality of alkyl radicals, containing at least 12 carbon atomsdirectly into the benzene nucleus of the benzyl chloride, and thenreacting the resulting alkylated benzyl chloride with a tertiary amine.

Another method for producing germ-counteracting agents encompassedwithin the present invention comprises reacting toluene with an olefin,under alkylating conditions, or with an alkyl halide pursuantto theFriedel-Craits synthesis toproduce an .allrylated toluene in which thealkyl radical or alkyl radicals contain a total of at least 11 carbonatoms. The resulting compound is then chlorinated under conditions suchas to replace a hydrogen-of the-methyl group of the alkylated toluenewith chlorine, after which the product is reacted with a tertiary amine.Where two chlorine atoms per mol are introduced, and then saidchlorinated compound is reacted with pyridine, an alkenylbenzylpyridinium chloride derivative is produced.

Another method which may be utilized with good results comprisesreacting a previously produced alkylated aromatic hydrocarbon compoundsuch as benzene or toluene with a halomethyl ether and then reacting theresulting compound with a tertiary amine. The halomethyl ether, forexample, bromomethyl ether, iodomethyl ether or chloromethyl ether,serves inefiect as a reservoir or equivalent of formaldehyde and thecorresponding hydrohalic acid.

Still another method which may be utilized for the preparation ofgerm-counteracting agents of the present invention is as follows: Anaromatic quaternary ammonium derivative comprising a benzyl group,- e.g.

may be alkylated with an olefin or an alkyl halide to introduce into thearomati-cring an aliphatic radical or radicals containing at least 12carbon atoms.

A particularly preferred method involves reacting a previously producedalliylated benzene or alkylated alkyl substituted benzene, for instance.a keryloenzene whose 'lreryl group is derived from a petroleumhydrocarbon distillate, with glacial acetic acid in the presence ofparaformaldehyde or trioxy-methylene and in the presence .of ananhydrouscondensing agent as, for example, zinc chloride, ferric chloride, oraluminum chloride, the reaction being carried out at relatively lowtemperatures, for example, oftthe-orderof-Sil to 65 degrees 0., coolingbeing employed it necessary. In carrying out this reaction, thearorernentioned ingredients are intermixedand a brisk stream of dryhydrogen chloride gas is introduced into the stirred mixturewhileinaintaining it at the aforementioned temperatures with occasionalcooling, if necessary. The reaction mixture is then cooled, petroleumether added thereto, and the mixture is then allowed to settle. Thelower layer is discarded and the toplayer can be Washed with 16% sodiumhydroxide solution and then with water. The petroleum ether solution isthen dried over anhydrous sodium sulfate, theether is distilled oii, andthe residue mixed with pyridine or triethylamine or other tertiaryamines and heated to about 10:) degrees C. for the requisite period-oitime. The desired compound is readily recoverable irom the reactionmixture by appropriate solvent treatments, for example, through theutilization of petroleum ether.

The examples hereinafter set forth are illustrative or" the productionof germ-counteracting agents falling within the scope of the invention.As indicated above, it will be appreciated that other methods maybeutilized. It will also be understood that proportions of ingredients andtemperatures and times of reaction may be varled; that differentcombinations of reactants may be utilized; and that various processes ofpurification and therlike may be resorted to wherever found desirableor-convenient. These and other variations and modifications will beclear to those versed in the art inthe light of the guiding principleswhich are disclosed herein.

Example 1 (a) 80 grams of mono-lauryl benzene and 60 grams ofchloromethyl ether were dissolved in 100 cc. of carbon disulfide. To theWell stirred solution, cooled to 0 degrees 0., there were added,dropwise, 126 grams of anhydrous stannic chloride. The mixture turned.dark in color and two layers formed. The reaction mixture was thenagitated for 1 hour-while maintained at temperature of about 0 degrees.C. Agitation was continued until the reaction mixture reached roomtemperature whereupon said mixture was poured into icewater. The organiclayerwasseparated and the aqueous solution Was extracted with ligroin.The combined organic solutions were dried over calcium. chloride and.the solvents weredistilled from the solutionaiter filtration. Theresidueweighed grams.

(b) :15 CCAOI the residue, producedin-part (a) hereof, were admixed with1 0 cc. of pyridine. The mixture was heated. for 2 hours at 60degrees-C. and-was then set aside for-about 2 days at room temperature.The resultin viscous liquid reaction mixture was treated with dry ethylether whereupon a white solid" precipitated.

It comprised essentially a compound having the formula:

CnHzr-QCHz-IET Example 2 "The lower layer which contained practicallyall of the zinc was discarded. The top layer was washed with 80 grams ofa sodium hydroxide solution and then with 100 cc. of water. Thepetroleum ether solution was then dried over anhydrous sodium sulfateand the solvent distilled off. The weight of the residue was 120 grams.This residue was then admixed with 27 grams of pyridine and the mixturewas heated to 100 degrees C. for 90 minutes. The'resulting viscousliquid was poured into 200 cc; of petroleum ether and agitatedvigorously. The petroleum ether was poured off and the residual materialwas triturated with petroleum ether. This treatment was repeated untilthe compound was converted into a brittle powder. The solid was filteredoff by suction and kept in a desiccator. The yield was 90 grams.

The solid dodecyl naphthylmethylpyridinium chloride is readily solublein water.

The aliphatic (including cycloaliphatic) radical represented by R in thegeneral formulae set forth above may be straight chain or branchedchain, substituted or unsubstituted, and saturated .or unsaturated. Itis particularly preferred that it be a straight chain, saturated alkylradical containin from 12 to 18 carbon atoms, especially from 12 to 16carbon atoms. Representative examples of such radicals are dodecyl,tetradecyl, hexadecyl, octadecyl, Z-butyloctyl, 2- butyltetradecyl,mixtures thereof, or mixtures derived from petroleum hydrocarbons, andthe like. Olefins which may, for example, be used as a source of alkylradicals include, for example,

pressure distillate, cracked distillate, and olefin polymers and thelike, such olefins containing from 12 to 18 carbon atoms and beingparticularly rich in 012 to C mono-olefins. Where the Friedel-Craftsreaction is used to introduce the alkyl radical into the aromatichydrocarbon nucleus, the corresponding alkyl halides preferably areutilized. Alkylations may be effected with catalysts such as HF, BFs,ZnClz, FeCla, SnCh, sulphuric acids, phosphoric acids, activated clays,and others.

The radical represented by Ar in the general formula set forth above maybe benzene or naphthalene or alkyl-substituted benzenes or naphthalenesas, for example, toluene, ethyl benzene and isopropyl benzene, isopropylnaphthalene, butyl naphthalene and the like. Particularly satisfactoryresults are obtained where the Ar radical is an unsubstituted benzene ornaphthalene radical.

The tertiary amines which are utilized in the preparation of thegerm-counteracting agents to 6 l introduce the quaternary ammoniumradical therein may be selected from a large group, including aliphaticamines and aromatic amines,

representative examples of which are trialkyl amines such astrimethylamine, triethylamine, tributylamine, dimethyl monoethyl amine,methyl morpholine, alkyl esters of N -substituted amino acids, dibutylmonoethyl amine; alkylaryl amines such as those having one alkyl and two'aryl groups or two alkyl and one aryl groups, examples of which arebenzyl morpholine, dibenzyl methyl amine, and diethyl aniline;heterocyclic amines such as pyridine and its homologues, quinolines,ocand B-picoline, N- substituted pyrroles, and substituted heterocyclicamines. Pyridine is particularly satisfactory in most cases. In general,the tertiary amine advaritageously contains at most 10 carbon-atoms.

As indicated by the various examples, the negative radical or anion oracid-forming or saltforming anionic radical in the quaternary ammoniumradical is preferably halogen. It may, however, be OH, HSOr, N03",acetate, borate,

propionate,

(311308 0 a, OHr-S 04- or some other organic or inorganic anion of solu-As a general rule, the comoilizing character. pounds are particularlysatisfactory where the anion is chlorine.

The germ-counteracthi agents which are used in accordance with thepresent invention have the particularly desirable features of possessingnot only exceptionally good germ-counteracting properties but, inaddition, they possess, in gen- Phenol Compound Organism Coefficlent (l)Lauryl benzyl pyridinium chloride. Staph. au1eus. 690 o E. typhi 570 (2)Lauryl ben ltriethyl ammonium chloride Staph. aureus.... 670 Do E typhi440 Where the germ-=counteracting agents of the present invention areused primarily for their germ-counteracting properties, they arepreferably used in the form of dilute aqueous solutions, for example,0.005% to 0.1%, with or without modifying agents as, for instance,buffers or the like to effect control of pH. Where used for hair shampooor like purposes, they are used in at least 6% aqueous solutions andpreferably in from 10% to 15% aqueous solutions. In any event, it isadvantageous to market the germcounteracting agents in the form ofconcentrates, for example, aqueous solutions containing from about 25%to about 40% of the germ-counteracting agents, depending upon thesolubility of the particular agents selected. In use, such concentratesmay be diluted to a degree suitable for the particular purpose in view.While it is preferred to utilize the germ-counteracting agents in themanner indicated above, it will be understood that they may be employedin the form of oleaginous solutions, powders, emulsions, solutions inorganic solvents such as alcohol, and

7, the like. large variety of products such as mouth washes,dentifrices, hair tonics, ointments and salves, lipsticks, cough drops,nose drops, disinfectant preparations, foot powders, etc. In theproduction of powders, I have found it to be desirable to admix thegerm-counteracting agents, in the form of strong aqueous solutions, withdry, inert carriers, preferably inorganic salts in anhydrous conditionbut which salts have the property of taking up water as water ofcrystallization.

It "will be understood that individual ones of the germ-counteractingagents of the present invention or mixturesof two or more of them may beemployed with or without previously known germ-counteracting agentswhich are compatible therewith.

While the invention has been described in detail, the scope thereof isnot to be limited other than-is set forth in the claims.

This application is a continuation-in-part of my prior applicationSerial No. 702,893, filed October 12, 1946, which, in turn, is acontinuaticn-in-part of application Serial No. 572,963, filed January15, 1945, both now abandoned.

What I claim as new and desire to protect by Letters Patent of theUnited 'States is:

1. A germ-counteracting agent having the where R is an alkyl radicalcontaining from 12 to 16 carbon atoms, Ar is a benzene hydrocarbonradical, and A is an anion selected from the group consisting ofchlorine, bromine and iodine.

2'. Dodecyl benzyl pyridinium chloride having the following structuralformula 3. Dodecyl alkyl benzyl pyridinium chloride having the formulaQ' IQ 0121125 01 alkyl 4. A germ-counteracting agent having the formulaThey may also be incorporated into a where R is an alkyl groupcontaining from 12 to 18 carbon atoms, Ar is a radical selectedfrom thegroup consisting of benzene and alkyl-substituted benzene in which thenumber of said last-mentionedalkyl groups does not exceed 3 and in whichthe number of carbon atoms in each of said last-mentioned alkyl radicalis from 1 to 4, NER1 is a tertiary amine having a total of not more than10 carbon atoms and containing only carbon, hydrogen and nitrogen andselected from the group consisting of trimethylamine, triethylamine,dimethyl monoethyl amine, dibutyl mcnoethyl amine, methyl benzyl amines,and pyridine, and A is a salt-forming anionic radical.

5. A germ-counteracting agent in accordance with claim 4, wherein R isdodecyl, and A is chlorine.

6. A germicidal agent having the formula R1 ---CH2-IL\T/'-R2 A Ra 0 31where R is an alkyl' radical containing from 12 to 1.8 carbonatoms,.-alky1 is an alkyl radical containing from 1 to 4 carbon atoms,17. isv an integer from 1 to 3, R1, RzandRa are. alkyl radicals eachcontaining from 1 to 5' carbon atoms, and A'is a salt-forming anionicradical.

7. A germicidal agent having the formula R ARs Where R isv an alkylradical containing from 12 to 18 carbon atoms, R1, R2 and R3 are allay-lradicals each containing from 1 to 5 carbon atoms, and A is asalt-forming anionic radical.

References Cited in the file of this patent UNITED STATES PATENTS NumberName Date 2,314,111 Tucker Mar. 16, 1943 2,609,270 Couper -Sept.--2, 1952 FOREIGN PATENTS Number Country Date 499,203 Great-Britain Jan. 16,1939 OTHER REFERENCES Stewart, Soap and Sanitary Chemicals, pp. 124 to127, Apr. 1950.

4. A GERM-COUNTERACTING AGENT HAVING THE FORMULA